Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease

Gastroenterology. 2003 Jun;124(7):1774-85. doi: 10.1016/s0016-5085(03)00382-2.


Background & aims: Steroid-refractory Crohn's disease responds to therapy with the chimeric anti-tumor necrosis factor (TNF)-alpha antibody infliximab. Etanercept, a recombinant TNF receptor/immunoglobulin G fusion protein, is highly effective in rheumatoid arthritis but not in Crohn's disease. Because both infliximab and etanercept are TNF-alpha-neutralizing drugs, we investigated the differences in TNF-alpha-neutralizing capacity and human lymphocyte binding and apoptosis-inducing capacity of both molecules.

Methods: We used a nuclear factor kappaB reporter assay and a cytotoxicity bioassay to study TNF-alpha neutralization by infliximab and etanercept. Lymphocyte binding and apoptosis-inducing capacity was investigated using fluorescence-activated cell sorter analysis, annexin V staining, and cleaved caspase-3 immunoblotting using mixed lymphocyte reaction-stimulated peripheral blood lymphocytes (PBL) from healthy volunteers and lamina propria T cells from patients with Crohn's disease.

Results: Both infliximab and etanercept neutralized TNF-alpha effectively. Infliximab bound to activated PBL and lamina propria T cells, whereas binding of etanercept was equal to a nonspecific control antibody. Infliximab but not etanercept induced peripheral and lamina propria lymphocyte apoptosis when compared with a control antibody. Infliximab activated caspase 3 in a time-dependent manner, whereas etanercept did not.

Conclusions: Although both infliximab and etanercept showed powerful TNF-alpha neutralization, only infliximab was able to bind to PBL and lamina propria T cells and subsequently to induce apoptosis of activated lymphocytes. These data may provide a biological basis for the difference in efficacy of the 2 TNF-alpha-neutralizing drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Apoptosis / drug effects*
  • Caspase 3
  • Caspases / metabolism
  • Cells, Cultured
  • Complement Activation
  • Crohn Disease / drug therapy*
  • Crohn Disease / immunology
  • Etanercept
  • Granzymes
  • Humans
  • Immunoglobulin G / metabolism
  • Immunoglobulin G / pharmacology*
  • Immunoglobulin G / therapeutic use
  • Infliximab
  • Intestinal Mucosa / immunology*
  • Lymphocyte Activation
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Serine Endopeptidases / biosynthesis
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / pathology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Monoclonal
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Etanercept